Criteria
Modified Ann Arbor staging system for NHL[115]
Stage I: Single lymph node group
Stage II: Multiple lymph node groups on same side of diaphragm
Stage III: Multiple lymph node groups on both sides of diaphragm
Stage IV: Multiple extranodal sites or lymph nodes and extranodal disease (an X denotes extranodal disease bulk >10 cm)
The following are added to the stage where relevant:
E: extranodal extension or single isolated site of extranodal disease
A: absence of symptoms
B: presence of B symptoms (weight loss >10% of body weight within 6 months of diagnosis; fever; and drenching night sweats)
Lugano modification of Ann Arbor staging system (for primary nodal lymphomas)[81]
Stage I: One node or group of adjacent nodes
Stage IE: Single extranodal lesions without nodal involvement
Stage II: Two or more nodal groups on the same side of the diaphragm
Stage IIE: Stage I or II by nodal extent with limited contiguous extranodal involvement
Stage II bulky: Two or more nodal groups on the same side of the diaphragm (i.e., stage II) with 'bulky' disease
Stage III: Nodes on both sides of the diaphragm; nodes above the diaphragm with spleen involvement
Stage IV: Additional noncontiguous extralymphatic involvement
International Prognostic Index (IPI)[116]
A prognostic scoring system for patients with aggressive NHL (e.g., diffuse large B-cell lymphoma [DLBCL]) based on the following risk factors:
Age >60 years
Serum lactate dehydrogenase (LDH) level >1 times normal
Performance status 2-4
Stage III-IV disease
Extranodal involvement >1 site
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0 or 1
Low-intermediate risk: 2
High-intermediate risk: 3
High risk: 4 or 5
Age-adjusted International Prognostic Index (IPI)[116]
An age-adjusted version of the IPI prognostic scoring system for patients aged ≤60 years based on the following risk factors:
Stage III-IV disease
Serum LDH level >1 times normal
Performance status 2-4
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0
Low-intermediate risk: 1
High-intermediate risk: 2
High risk: 3
Stage-modified International Prognostic Index (smIPI)[117]
A stage-modified version of the IPI prognostic scoring system for patients with localised (stage I or II) disease, based on the following risk factors:
Age >60 years
Stage II disease
Serum LDH level >1 times normal
Performance status 2-4
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0 or 1
High risk: 2-4
NCCN International Prognostic Index (IPI)[118]
A modified version of the IPI prognostic scoring system (using data from the NCCN NHL database in the rituximab era) based on the following risk factors (with assigned scores):
Age >40 to ≤60 years (score: 1)
Age >60 to ≤75 years (score: 2)
Age >75 years (score: 3)
LDH ratio* >1 to ≤3 (score: 1)
LDH ratio* >3 (score: 2)
Ann Arbor stage III-IV (score: 1)
Extranodal disease (in bone marrow, central nervous system, liver/gastrointestinal tract, or lung) (score: 1)
Eastern Cooperative Oncology Group (ECOG) performance status ≥2 (score: 1)
*Normalised LDH (ratio ≤1) used as a reference.
Patients are risk-stratified based on total score:
Low risk: 0 or 1
Low-intermediate risk: 2 or 3
High-intermediate risk: 4 or 5
High risk: ≥6
Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria[119]
Criteria used to assess tumour burden in patients with follicular lymphoma. Patients with any of the following are classified as having a high tumour burden:
Involvement of ≥3 nodal sites, each with a diameter of ≥3 cm
Any nodal or extranodal tumour mass with a diameter of ≥7 cm
B symptoms
Splenomegaly
Pleural effusions or peritoneal ascites
Cytopenias (leukocytes <1.0 × 10⁹/L and/or platelets <100 × 10⁹/L)
Leukaemia (>5.0 × 10⁹/L malignant cells)
Follicular lymphoma International Prognostic Index 1 (FLIPI-1)[120]
A prognostic scoring system for patients with follicular lymphoma (developed before the availability of rituximab) based on the following risk factors:
Age >60 years
Ann Arbor stage III-IV
Haemoglobin level <12 g/dL
Serum LDH > upper limit of normal (>ULN)
Number of nodal sites >4
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0 or 1
Intermediate risk: 2
High risk: 3-5
Follicular lymphoma International Prognostic Index 2 (FLIPI-2)[98]
An updated version of the FLIPI-1 prognostic scoring system for patients with follicular lymphoma (developed after the availability of rituximab) based on the following risk factors:
Age >60 years
Haemoglobin level <12 g/dL
Longest diameter of largest involved lymph node >6 cm
Beta-2 microglobulin level >ULN
Bone marrow involvement present
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0
Intermediate risk: 1-2
High risk: 3-5
Central nervous system (CNS) International Prognostic Index (CNS-IPI)[121]
A prognostic tool used to estimate the risk of CNS relapse/progression in patients with DLBCL based on the following risk factors:
Kidney and/or adrenal glands involved
Age >60 years
LDH > normal
ECOG performance status >1
Stage III-IV disease
Extranodal involvement >1 site
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0 or 1
Intermediate risk: 2-3
High risk: 4-6
Mantle cell lymphoma International Prognostic Index (MIPI)[122]
A prognostic scoring system for patients with advanced stage mantle cell lymphoma, based on the following risk factors:
Age
<50 years: 0
50-59 years: 1
60-69 years: 2
≥70 years: 3
ECOG performance status
0-1: 0
2-4: 2
LDH ratio (weighted according to ULN)
<0.67: 0
0.67 to 0.99: 1
1.00 to 1.49: 2
≥1.50: 3
WBC count (10⁹/L)
<6.70: 0
6.70 to 9.99: 1
10.00 to 14.99: 2
≥15.00: 3
Patients are risk-stratified based on total score:
Low risk: 0-3
Intermediate risk: 4 or 5
High risk: 6-11
The MIPI score can be modified to incorporate data on Ki-67 (a proliferation marker) if available from biopsy studies (to calculate the biological MIPI).
Marginal zone lymphoma International Prognostic Index (MZL-IPI)[123]
A prognostic scoring system for patients with marginal zone lymphoma (MZL), based on the presence of the following risk factors:
LDH level above the upper limit of normal
Haemoglobin <12 g/dL
Absolute lymphocyte count <1 × 10⁹/L
Platelet count <100 × 10⁹/L
MZL subtype (nodal or disseminated)
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0
Intermediate risk: 1-2
High risk: 3-5
Burkitt's lymphoma International Prognostic Index (BL-IPI)[124]
A prognostic scoring system for patients with Burkitt's lymphoma, based on the following risk factors:
Age ≥40 years
ECOG performance status 2-4
Serum LDH >3 ULN
CNS involvement
Patients are risk-stratified based on the number of risk factors present:
Low risk: 0
Intermediate risk: 1
High risk: 2-4
Deauville criteria[83]
The Deauville criteria can be used to assess interim and end-of-treatment response in patients with certain NHLs (e.g., DLBCL, peripheral T-cell lymphomas). It is a five-point scale that assesses fluorodeoxyglucose (FDG) uptake at involved sites relative to the mediastinum and liver, as visualised on positron emission tomography/computed tomography (PET/CT) scan:
No FDG uptake: score = 1
FDG uptake ≤ mediastinum: score = 2
FDG uptake > mediastinum but ≤ liver: score = 3
FDG uptake moderately higher than liver: score = 4
FDG uptake markedly higher than liver and/or new lesions: score = 5
New areas of FDG uptake unlikely to be related to lymphoma: score = X
Patients with a negative PET/CT (i.e., Deauville score 1-3) are considered to have a complete metabolic response. Patients with a positive PET/CT (i.e., Deauville score 4 or 5) are considered to have a partial metabolic response.
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